Omics · study · 2026
CD44 IN MYELOID CELLS IS A MAJOR DRIVER OF LIVER INFLAMMATION AND INJURY IN ALCOHOL-RELATED LIVER DISEASE [CD44_KO_Ethanol]
Listed in NCBI GEO
Background and Aims: Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-related steatohepatitis (ASH).
Description
CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the ALD context. We therefore studied its contribution to ASH development in mice and its expression in ALD patients.
Approach and Results: Here, we report that liver CD44 expression is associated with liver injury and inflammation and its deficiency (Cd44-/-) partially protected mice upon chronic plus binge ethanol feeding (CPB-EtOH). CD44 deletion in myeloid cells (Cd44myel-KO) recapitulated the same protective effects associated with reduced inflammatory monocyte infiltration and neutrophil activation in the liver and diminished blood neutrophil-lymphocyte ratio (NLR).
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CD44-deficient neutrophils displayed reduced PMA-induced inflammatory mediator expression and increased phagocytosis of live bacteria. Cd44myel-KO mice were also protected against hepatic steatosis mediated by CPB-EtOH or chronic ethanol feeding, due in part to increased SIRT1 mediated fatty acid beta-oxidation. CD44 neutralization with antibodies strongly decreased liver injury and inflammation (hepatic neutrophil frequency) and blood NLR upon CPB-EtOH.
In samples from ALD patients, hepatic CD44 expression increased with ALD severity, correlated with hepatic TNFα and CD11b expression, and CD44-expressing neutrophils were enriched in alcohol-associated hepatitis. Conclusions: Human and experimental evidence supports CD44 as a marker of hepatic inflammation in ALD. In addition, CD44 modulates neutrophil mobilization and functions and its targeting partially prevents liver inflammation and injury in the context of acute-on-chronic alcohol drinking.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE295nnn/GSE295747 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295747 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1256305 ncbi.nlm.nih.gov/bioproject/PRJNA1256305 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE295747 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |